The role of Potassium in Cobalamin-Dependent Methionine Synthase

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Abstract

The essential nutrient folate is used by the body to carry out reactions necessary
for the production and maintenance of cells. If an enzyme that plays a role in the folate
pathways of the body is not functioning to its full capacity due to a common mutation or
polymorphism, an individual with this genetic defect may have an increased chance of
developing a disease associated with folate deficiency, especially if they already have a
low nutritional intake of folate. It is important to identify these polymorphisms, and to
discover at what frequency they occur in the population. A major enzyme in the folate
pathway is cobalamin-dependant methionine synthase (MetH). Recently it was
discovered that the structure of MetH contains a potassium ion whose binding region is
conserved in similar enzymes across different species levels. Because of this
conservation, it was predicted that potassium is important for the function of MetH. If
true, a genetic defect in the potassium binding would lead to the imbalance of folate
metabolism, leaving individuals more at risk for disease. In this study, it was . shown that
the presence of potassium is indeed needed for the full activity of MetH. In addition, the
enzyme was found to be most active in concentrations of potassium similar to that found
inside the cell, making these findings physiologically relevant. Finally, it was found that
the specific component of the reaction in which potassium is likely to be involved is
catalysis of the methyl transfer during the reaction.